Ceramic fusion implants and compositions

ABSTRACT

Bone graft substitute compositions are provided for promoting new bone growth and arthrodesis. The compositions include a carrier for controlled delivery of osteoinductive factors. In one embodiment, the carriers include a biphasic calcium phosphate ceramic having between about 2-40% hydroxyapatite and about 98-60% tricalcium phosphate by volume, and a calcium/phosphorous ratio of between about 1.50 to about 1.60. The invention also includes osteoinductive compositions including the carriers and an effective amount of a bone morphogenetic protein dispersed within the ceramic. The composition has a weight ratio of protein to ceramic of no more than about 1:200. In a specific embodiment, the weight ratio of protein to ceramic is between about 1:200 and about 1:2000. Spinal implants (10) are also provided which include a body (11) having a wall (12) sized for engagement within a space (S) between adjacent vertebrae (V) to maintain the space (S) and a confining matrix (13) for confining new bone growth to the body (11). The matrix (13) includes a biphasic calcium phosphate ceramic which degrades at a rate to provide calcium and phosphate for the new bone growth without reduced density of bone adjacent the space and an effective amount of a substantially pure osteogenic factor bound to the ceramic.

FIELD OF THE INVENTION

The present invention relates to bone graft substitute compositions andimplants for new bone formation and arthrodesis. In specificapplications of the invention the compositions include biocompatiblecalcium phosphate ceramics in synergistic combination with osteogeniccompositions.

BACKGROUND OF THE INVENTION

Many techniques have been developed for correcting bone defects andvoids In one approach, the void is filled with a bone paste or bonecompound. In other techniques, the void is filled with a corallinesubstance. In these approaches, one goal is to induce the formation ofnew bone from the patient's existing bone to fill the void or repair thedefect.

Aspects of these techniques have also been borrowed for application inother orthopedic procedures, such as spinal fusion. Spinal fusion isindicated to provide stabilization of the spinal column for painfulspinal motion and disorders such as structural deformity, traumaticinstability, degenerative instability, and post-resection iatrogenicinstability. Fusion, or arthrodesis, is achieved by the formation of anosseous bridge between adjacent motion segments. This can beaccomplished within the disc space, anteriorly between contiguousvertebral bodies or posteriorly between consecutive transverseprocesses, laminae or other posterior aspects of the vertebrae.

An osseous bridge, or fusion mass, is biologically produced by the bodyupon skeletal injury. This normal bone healing response is used bysurgeons to induce fusion across abnormal spinal segments by recreatingspinal injury conditions along the fusion site and then allowing thebone to heal. A successful fusion requires the presence of osteogenic orosteopotential cells, adequate blood supply, sufficient inflammatoryresponse, and appropriate preparation of local bone. This biologicalenvironment is typically provided in a surgical setting bydecortication, or removal of the outer, cortical bone to expose thevascular, cancellous bone, and the deposition of an adequate quantity ofhigh quality graft material.

A fusion or arthrodesis procedure is often performed to treat an anomalyinvolving an intervertebral disc. Intervertebral discs, located betweenthe endplates of adjacent vertebrae, stabilize the spine, distributeforces between vertebrae and cushion vertebral bodies. A normalintervertebral disc includes a semi-gelatinous component, the nucleuspulposus, which is surrounded and confined by an outer, fibrous ringcalled the annulus fibrosis. In a healthy, undamaged spine, the annulusfibrosis prevents the nucleus pulposus from protruding outside the discspace.

Spinal discs may be displaced or damaged due to trauma, disease oraging. Disruption of the annulus fibrosis allows the nucleus pulposus toprotrude into the vertebral canal, a condition commonly referred to as aherniated or ruptured disc. The extruded nucleus pulposus may press onthe spinal nerve, which may result in nerve damage, pain, numbness,muscle weakness and paralysis. Intervertebral discs may also deterioratedue to the normal aging process or disease. As a disc dehydrates andhardens, the disc space height will be reduced leading to instability ofthe spine, decreased mobility and pain.

Sometimes the only relief from the symptoms of these conditions is adiscectomy, or surgical removal of a portion or all of an intervertebraldisc followed by fusion of the adjacent vertebrae. The removal of thedamaged or unhealthy disc will allow the disc space to collapse.Collapse of the disc space can cause instability of the spine, abnormaljoint mechanics, premature development of arthritis or nerve damage, inaddition to severe pain. Pain relief via discectomy and arthrodesisrequires preservation of the disc space and eventual fusion of theaffected motion segments.

Bone grafts are often used to fill the intervertebral space to preventdisc space collapse and promote fusion of the adjacent vertebrae acrossthe disc space. In early techniques, bone material was simply disposedbetween the adjacent vertebrae, typically at the posterior aspect of thevertebrae, and the spinal column was stabilized by way of a plate or rodspanning the affected vertebrae. Once fusion occurred, the hardware usedto maintain the stability of the segment became superfluous and was apermanent foreign body. Moreover, the surgical procedures necessary toimplant a rod or plate to stabilize the level during fusion werefrequently lengthy and involved.

It was therefore determined that a more optimal solution to thestabilization of an excised disc space is to fuse the vertebrae betweentheir respective end plates, preferably without the need for anterior orposterior plating. There have been an extensive number of attempts todevelop an acceptable intra-discal implant that could be used to replacea damaged disc and maintain the stability of the disc interspace betweenthe adjacent vertebrae, at least until complete arthrodesis is achieved.To be successful, the implant must provide temporary support and allowbone ingrowth. Success of the discectomy and fusion procedure requiresthe development of a contiguous growth of bone to create a solid massbecause the implant may riot withstand the cyclic compressive spinalloads for the life of the patient.

Many attempts to restore the intervertebral disc space after removal ofthe disc have relied on metal devices. U.S. Pat. No. 4,878,915 toBrantigan teaches a solid metal plug. U.S. Pat. Nos. 5,044,104;5,026,373 and 4,961,740 to Ray; U.S. Pat. No. 5,015,247 to Michelson andU.S. Pat. No. 4,820,305 to Harms et al., U.S. Pat. No. 5,147,402 toBohler et al. and U.S. Pat. No. 5,192,327 to Brantigan teach hollowmetal cage structures. Unfortunately, due to the stiffness of thematerial, some metal implants may stress shield the bone graft,increasing the time required for fusion to occur. Subsidence, or sinkingof the device into bone, is also a concern when metal implants areimplanted between vertebrae. Metal devices are also foreign bodies whichcan never be fully incorporated into the fusion mass. Moreover, fusionrates can be slower with metal implants as compared to graft.

Various bone grafts and bone graft substitutes have also been used topromote osteogenesis and to avoid the disadvantages of metal implants.Autograft is often preferred because it is osteoinductive. Bothallograft and autograft are biological materials which are replaced overtime with the patient's own bone, via the process of creepingsubstitution. Over time a bone graft virtually disappears unlike a metalimplant which persists long after its useful life. Unfortunately, theuse of autograft presents several disadvantages. Autograft is availablein only limited quantities. The additional surgery also increases therisk of infection and blood loss and may reduce structural integrity atthe donor site. Furthermore, some patients complain that the graftharvesting surgery causes more short-term and long-term pain than thefusion surgery.

Allograft material, which is obtained from donors of the same species,is more readily obtained. However, allograft is also disadvantageousbecause of the risk of disease transmission and immune reactions as wellas religious objections. Furthermore, allogenic bone has limitedosteoinductive potential compared to autogenous bone and therefore mayprovide only temporary support. The slow rate of fusion usingallografted bone can lead to collapse of the disc space before fusion isaccomplished.

Both allograft and autograft present additional difficulties. Graftalone may not provide the stability required to withstand spinal loads.Internal fixation can address this problem but presents its owndisadvantages such as the need for more complex surgery as well as thedisadvantages of metal fixation devices. Also, the surgeon is oftenrequired to repeatedly trim the graft material to obtain the correctsize to fill and stabilize the disc space. This trial and error approachincreases the length of time required for surgery. Furthermore, thegraft material usually has a smooth surface which may not provide a goodfriction fit between the adjacent vertebrae. Slippage of the graft maycause neural and vascular injury, as well as collapse of the disc space.Even where slippage does not occur, micromotion at the graft/fusion-siteinterface may disrupt the healing process that is required for fusion.

Due to the need for safer bone graft materials, bone graft substitutes,such as bioceramics, have recently received considerable attention. Thechallenge has been to develop a bone graft substitute which avoids thedisadvantages of metal implants and bone grafts while capturing theadvantages of both. Calcium phosphate ceramics are biocompatible and donot present the infectious or immunological concerns of allograftmaterials. Ceramics may be prepared in any quantity which is a greatadvantage over autograft bone graft material. Furthermore, bioceramicsare osteoconductive, stimulating osteogenesis in bony sites. Bioceramicsprovide a porous matrix which further encourages new bone growth.Unfortunately, ceramic implants typically lack the strength to supporthigh spinal loads and therefore require separate fixation before thefusion.

Of the calcium phosphate ceramics, hydroxyapatite (HA) and tricalciumphosphate (TCP) ceramics have been most commonly used for bone grafting.Hydroxyapatite is chemically similar to inorganic bone substance andbiocompatible with bone. However, it is slowly degraded. β-tricalciumphosphate is rapidly degraded in vivo and is too weak to provide supportunder the cyclic loads of the spine until fusion occurs. Developing animplant having the biomechanical properties of metal and the biologicalproperties of bone without the disadvantages of either has beenextremely difficult or impossible.

In any application involving the formation of new bone, the orthopedicsurgeon is concerned first that the new bone formation be complete, andsecond that the creation of the new bone occur as rapidly as possible.In the case of spinal fusion, another concern is that the spinalsegments be adequately supported and stabilized until arthrodesisoccurs. Orthopedics practitioners have long sought compositions andimplants that provide optimum performance to address these and othercritical concerns.

Thus far, a need remains for a bone graft substitute composition thatprovides this optimum performance and that can have wide applicabilityin the treatment of orthopedic conditions. In the field of spinalfusion, a need has remained for fusion devices and methods whichstimulate bone ingrowth and avoid the disadvantages of metal implantsyet provide sufficient strength to support the vertebral column untilthe adjacent vertebrae are fused.

SUMMARY OF THE INVENTION

In accordance with the invention, bone graft substitute compositions areprovided for new bone formation and spinal arthrodesis. The compositionsinclude a carrier for controlled delivery of bone growth inductivefactors, such as bone morphogenetic proteins. In one aspect of theinvention, the carriers include a biphasic calcium phosphate ceramichaving between about 2-40% hydroxyapatite and about 98-60% tricalciumphosphate by volume and preferably a calcium/phosphorous ratio ofbetween about 1.50 to about 1.60.

In other embodiments, the carriers preferably include a biphasic calciumphosphate ceramic having between about 5-20% hydroxyapatite and about95-80% tricalcium phosphate by volume and most preferably about 20%hydroxyapatite and about 80% tricalcium phosphate.

The invention also contemplates osteoinductive compositions includingthe carriers and an effective amount of a bone growth inductive factor,such as substantially pure bone morphogenetic protein, dispersed withinthe ceramic. The composition preferably has a weight ratio of factor toceramic of no more than about 1:200. In specific embodiments, the weightratio of factor to ceramic is between about 1:200 and about 1:2000.

Spinal implants are also provided which include a body having a wallsized for engagement within a space between adjacent vertebrae tomaintain the space and a confining matrix for confining new bone growthto the matrix. The matrix includes a biphasic calcium phosphate ceramicwhich degrades at a rate to provide calcium and phosphate for the newbone growth without reduced density of adjacent host bone and aneffective amount of a substantially pure osteogenic factor bound to theceramic.

One object of the present invention is to provide a bone graftsubstitute composition that provides a stable matrix for rapid growth ofnew bone into a space, such as a bone defect, void or fusion site. Amore specific object of this invention is to provide spinal implants andcompositions for arthrodesis of a motion segment which exploit all ofthe advantages of ceramic implants while avoiding the correspondingdisadvantages. Another object of the invention is to provide a spinalimplant which restores the intervertebral disc space and supports avertebral column while promoting bone ingrowth.

One benefit of this invention is that it provides a synergisticcomposition of a bioceramic and an osteoinductive factor. The ceramicprovides a stable scaffold for bone ingrowth and through-growth whilethe osteoinductive factor induces bone growth to speed the fusion rate.The increased speed of fusion allows the use of a bioceramic without theneed for metal cages or internal fixation.

The ceramic also advantageously provides a source of calcium andphosphate to the fusion site. Another advantage is that the ceramicprovides a matrix for confining induced bone growth to the fusion siteto avoid bone growth in inappropriate locations. Other objects andfurther benefits of the present invention will become apparent topersons of ordinary skill in the art from the following writtendescription and accompanying figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side perspective view of a spinal implant according to thisinvention.

FIG. 2 is a side elevational view of a portion of a spine having thespinal implant of FIG. 1 implanted in the intervertebral space.

FIG. 3 depicts a kidney-shaped spinal implant according to anotherembodiment of this invention.

FIG. 4 is a side elevational view of another spinal implant according tothis invention.

FIG. 5 is a side perspective view of a portion of the spine showing twospinal implants as shown in FIG. 1 and implanted in the intervertebralspace.

FIG. 6 is a side elevational view of a section of the spine showingspinal implants implanted bilaterally.

DESCRIPTION OF THE PREFERRED EMBODIMENT

For the purposes of promoting an understanding of the principles of theinvention, reference will now be made to certain embodiments thereof andspecific language will be used to describe the same. It willnevertheless be understood that no limitation of the scope of theinvention is thereby intended, such alterations, further modifications,and applications of the principles of the invention as illustratedherein being contemplated as would normally occur to one skilled in theart to which the invention relates.

The present invention provides synergistic combinations of bioceramicswith osteoinductive factors, such as bone morphogenetic proteins (BMP).The combination of the osteoinductive factor with a calcium phosphatecarrier provides controlled delivery of the osteoinductive material byits natural binding to calcium phosphate and entrapped within the poresof the ceramic.

This invention provides carriers for osteoinductive factors which areoptimized in terms of composition, bioactivity, porosity, pore size,protein binding potential, degradability and strength for use in bothload bearing and non-load bearing grafting applications. The properselection of bioceramic also provides slow degradation of the ceramicwhich results in a local source of calcium and phosphate for boneformation. Therefore, new bone can be formed without calcium andphosphate loss from the host bone surrounding the fusion site. Thisavoids fusion at the expense of reduced bone mineral density of adjacenthost bone. The confining matrix of the ceramic prevents induced bonegrowth outside the carrier structure. The calcium phosphate carrierstructure maintains a space for bone formation to occur and alsoprovides a scaffold for bone ingrowth. The quicker fusion rates providedby this invention due to the osteoinductive factor compensate for theless desirable biomechanical properties of bioceramics and makes the useof internal fixation and metal interbody fusion devices unnecessary. Thedevices of this invention are not required to support the cyclic loadsof the spine for very long because of the quick fusion rates whichreduce the biomechanical demands on the implant.

In one embodiment, compositions are provided which include a carrier ormatrix for controlled delivery of bone morphogenetic proteins and otherbone growth inductive factors. The carriers preferably include abiphasic calcium phosphate (BCP) ceramic having hydroxyapatite andtricalcium phosphate. The ceramics can be prepared according to methodswhich are known in the art and can preferably include the application ofa pore forming agent to form a porous ceramic. Biphasichydroxyapatite/tricalcium phosphate (HA/TCP) is particularly preferred.In one specific embodiment, the bioceramics can be made according tomaterials commercially available from Sofamor Danek Group, B. P. 4-62180Rang-du-Fliers, France and Bioland, 132 Route d:Espagne, 31100 Toulouse,France.

Both hydroxyapatite (HA) and tricalcium phosphate (TCP) have been usedalone as bone graft substitutes. Hydroxyapatite acts as a scaffold fornew bone formation, but undergoes little or no resorption. Moreover, HAis generally radiopaque so that it is difficult for surgeons to assessthe progress of the new bone formation using x-rays. On the other hand,tricalcium phosphate has been found to resorb faster than the rate ofnew bone formation. Advantageously it has been discovered that biphasicceramics provide beneficial degradation rates while the problemsassociated with the use of HA or TCP alone.

The carriers of this invention have between about 2-40% hydroxyapatiteand about 98-60% tricalcium phosphate by volume, preferably betweenabout 5-20% HA and about 95-80% TCP. The most preferred ratio is about20% HA and about 80% TCP by volume. Although bone formation occurs whenthe carrier is comprised solely of tricalcium phosphate, the volume ofbone is significantly less when compared to a hydroxyapatite/tricalciumphosphate carrier. It has been found that the presence of slowerdegrading hydroxyapatite in the carrier is necessary to provide betterspace maintenance for bone formation than a carrier composed oftricalcium phosphate alone. Although the hydroxyapatite degrades moreslowly than the tricalcium phosphate, thereby providing a scaffold forcontinued new bone formation, too high a percentage of hydroxyapatiteimpedes the ability to monitor the progress of fusion. Therefore, acomposite of HA/TCP will provide a good temporary scaffold, and anoptimum ratio of HA to TCP will permit easier radiographic assessment ofthe new bone formation.

For example, carriers containing 60% hydroxyapatite and 40% tricalciumphosphate by weight have been evaluated but the resulting fusions aredifficult to evaluate as this combination appears radiopaque on X-raysfor long periods of time. Therefore, the optimum percentages ofhydroxyapatite and tricalcium phosphate of the present invention havebeen carefully designed to take the above factors into account. Otheradvantages of having a lower percentage of hydroxyapatite in the carrierinclude a significantly decreased manufacturing time of the ceramicusing standard precipitation methods carried out under basic pHconditions. For example, a three-fold greater reaction time is necessaryto produce a biphasic ceramic comprising 60% hydroxyapatite and 40%tricalcium phosphate by weight, compared to a ceramic containing 18%hydroxyapatite and 82% tricalcium phosphate by weight.

The calcium/phosphorus ratio of the ceramics is preferably between about1.50 to about 1.60, and most preferably 1.51. Compositions of thisinvention also include a pharmaceutically effective amount of a bonegrowth inductive factor, such as a substantially pure bone morphogeneticprotein, dispersed within the ceramic. Various bone growth inductivefactors are also contemplated, such as bovine extracted proteins,non-protein factors and DNA factors. Advantageously, due to the efficacyof the carrier, small quantities of the bone growth inductive factor canbe used very efficiently. The composition preferably has a weight ratioof factor to ceramic of no more than about 1:200. Preferably, the weightratio of factor to ceramic is between about 1:200 and about 1:2000. In aspecific embodiment in which the factor is a recombinant human bonemorphogenetic protein, the weight ratio is 1:1250.

The preferred osteoinductive factors are the recombinant human bonemorphogenetic proteins (rhBMPs) because they are available in unlimitedsupply arid do not transmit infectious diseases. Most preferably, thebone morphogenetic protein is a rhBMP-2, rhBMP-7 or heterodimersthereof. However, any bone morphogenetic protein is contemplatedincluding bone morphogenetic proteins designated as BMP-1 throughBMP-13. BMPs are available from Genetics Institute, Inc., Cambridge,Mass. and may also be prepared by one skilled in the art as described inU.S. Pat. No. 5,187,076 to Wozney et al.; U.S. Pat. No. 5,366,875 toWozney et al.; U.S. Pat. No. 4,877,864 to Wang et al.; U.S. Pat. No.5,108,922 to Wang et al.; U.S. Pat. No. 5,116,738 to Wang et al.; U.S.Pat. No. 5,013,649 to Wang et al.; U.S. Pat. No. 5,106,748 to Wozney etal.; and PCT Pat. Nos. WO93/00432 to Wozney et al.; WO94/26893 toCeleste et al.; and WO94/26892 to Celeste t al. All osteoinductivefactors are contemplated whether obtained as above or isolated frombone. Methods for isolating bone morphogenetic protein from bone aredescribed in U.S. Pat. No. 4,294,753 to Urist and Urist et al., 81 PNAS371, 1984.

The bone growth inductive factor may be supplied to the pores of theceramic in any suitable manner. The osteogenic factor, preferably BMP,may be provided in freeze-dried form and reconstituted in sterile water,physiological saline, collagen gel, or any other suitable liquid or gelcarrier. Any suitable medium or carrier capable of delivering theproteins to the pores of the implant is contemplated. Preferably themedium is supplemented with a buffer solution as is known in the art.The ceramic may be soaked in a solution containing the factor.Alternatively, the composition may be injected into the pores of theceramic. In other embodiments, the composition is dripped onto theceramic. In one specific embodiment of the invention, rhBMP-2 issuspended or admixed in a liquid carrier, such as water, saline orcollagen gel. The liquid is then dripped into the pores or the ceramicis immersed in a suitable quantity of the liquid, in either case for aperiod of time sufficient to allow the liquid to thoroughly soak thegraft.

The BCP ceramics of this invention are excellent carriers forosteoinductive factors such as bone morphogenetic proteins.Hydroxyapatite, which is very similar to the mineral phase of corticalbone, is an osteogenic factor bonding agent which controls the rate ofdelivery of proteins to the fusion site and contains osteoinductivefactors inside the carrier. The porous structure allows mesenchymalcells to migrate into the carrier. These cells are then transformed intobone forming cells, or osteoblasts, and ultimately deposit new boneinside the carrier. The calcium phosphate compositions in this inventionbind bone morphogenetic proteins and prevent BMP from prematurelydissipating from the device before fusion can occur. Retention of theBMP by the ceramic permits the protein to complete rapid bone formationand ultimately fusion across the disc space.

The BCP ratios of this invention result in more rapid and larger volumeof new bone formation which allows lower dosing of osteoinductivefactor. This invention exploits the discovery that HA and TCP havedifferential binding properties. Therefore this invention provides BCPratios which optimize the binding potential balanced with degradabilityand strength. The optimized ratios result in more rapid and superiorfusions. This is an improvement over prior art carriers which do noteffectively bind proteins such as BMP. In some cases, TCP ceramics havereleased the protein too rapidly and have not provided sustained dosingof the protein. This is also disadvantageous because it allows theprotein to escape the fusion site since the carrier scaffold is lost.The carriers of the present invention, however, protect the protein frombeing metabolized. This keeps a therapeutic level of protein at thefusion site.

This invention also provides ceramics having beneficial porositycharacteristics in the case where the ceramic is formed into a block orshaped body. A porosity of between about 60% and 80%, and preferablyabout 70%, offers maximal porosity for bone ingrowth while stillmaintaining the mechanical integrity of the ceramic. The ceramics ofthis invention have interconnecting porosity which provide excellentwettability and surface area for protein binding as well as an optimalmatrix structure for bone ingrowth. The pore size has also beenoptimized in this invention. The ceramics of this invention preferablyhave a pore size of between about 200 to about 600 microns. This poresize is optimal for bone ingrowth without compromising structuralintegrity.

Another significant advantage of this invention is that the BCP ceramicsprovide a confining matrix for confining new bone growth to the ceramicbody. This can be important for applications involving areas such as thespine where vital neural and vascular tissues are exposed andvulnerable. The invasion of BMP and other osteoinductive factors intoand around these tissues may cause serious complications.

In accordance with one aspect of the invention, the bone graftsubstitute composition is formed for introduction into a patient. Insome applications, the composition is provided in the form of a porousblock or body that is sized and shaped for introduction into a bonedefect or void. In other applications, the composition is provided ingranular form. This granular composition can be used to fill a void,disposed within the intradiscal space, or placed in the transverseinterval between adjacent vertebrae, for example.

In one specific application, the present invention also contemplatesspinal implants as depicted in FIGS. 1-5. Referring now to FIG. 1, aspinal implant 10 is provided which includes a body 11 having a wall 12sized for engagement within a space S between adjacent vertebrae V tomaintain the space S. The implant includes a confining matrix 13 forconfining new bone growth to the implant 10. The confining matrix 13includes pores 14 for containing the osteoinductive factor. The wall 12has a height h which corresponds to the height H of the space S. In oneembodiment, the height h of the wall 12 is slightly larger than theheight H of the intervertebral space S. The wall 12 is adjacent to andbetween a superior engaging surface 15 and an inferior engaging surface16 which are configured for engaging the adjacent vertebrae V as shownin FIG. 2.

The bodies contemplated by this invention may be any suitably sized andshaped body composed of a bioceramic, preferably a BCP ceramic. Ceramicscan be conveniently formed into virtually any shape. For example, thebody 21 of the spinal implant 20 may be kidney-shaped as shown in FIG.3. The shape is advantageous because it approximates the shape of avertebral endplate. Alternatively, a spinal implant 30 may be providedwhich comprises a generally rectangular body 31 as shown in FIG. 4. Oneadvantage of the embodiments of this invention is that they allowbilateral placement of spinal implants as shown in FIG. 5.

This invention contemplates spinal implants which can be implantedwithin a disc space as shown in FIGS. 2 and 5 and also spinal implantsfor posterolateral fusions as shown in FIG. 6. The spinal implant 30shown in FIG. 4 is particularly suited for this application. Referringto FIG. 6, the spinal implant 30 spans and contacts the transverseprocesses P of adjacent vertebrae V. The implant 30 maintains a space orpocket P above and across the transverse processes for new boneformation.

The composition of the ceramic will depend on the application. Spinalimplants require increased strength to support the cyclic loads of thespine until fusion occurs. The strength of these implants can beincreased by increasing the hydroxyapatite content of the ceramic or bysupplementing the implant with metal devices such as cages. Forposterolateral fusion applications which do not have the same strengthrequirements, the ceramic may have an increased tricalcium phosphatecontent. A Ca/P and HA/TCP ratio has been identified that balances allthe requirements of a carrier for BMP in non-load bearing fusionapplications, such as posterolateral fusions, or for use with a cage ormetal fixation in load bearing fusions. In some cases the TCP contentmay approach 100%.

Even in non-load bearing applications, strength of the ceramic is animportant consideration. The ceramic must be handled by the surgeon andmust resist compression by overlying muscles to maintain a space forbone formation. A minimal amount of HA, preferably about 5%, is requiredfor this purpose.

Advantageously, the spinal implants of the present invention may notrequire internal fixation. The implants are contained by the compressiveforces of the surrounding muscles. Temporary external mobilization andsupport of the instrumented and adjacent vertebral levels, with acervical collar, lumbar brace or the like, is generally recommendeduntil adequate fusion is achieved.

While the invention has been illustrated and described in detail in thedrawings and foregoing description, the same is to be considered asillustrative and not restrictive in character, it being understood thatonly the preferred embodiments have been shown and described and thatall changes and modifications that come within the spirit of theinvention are desired to be protected.

What is claimed is:
 1. A spinal implant, comprising:a body having anouter wall of a height sufficient for engagement within a space betweenadjacent vertebrae to maintain the space, a superior bone engagingsurface, an inferior bone engaging surface, a confining matrix betweensaid surfaces for confining new bone growth to said matrix, saidconfining matrix having pores and including a biphasic calcium phosphateceramic having between about 2-40% hydroxyapatite and between about98-60% tricalcium phosphate by volume; and a therapeutically effectiveamount of a bone growth inductive factor entrapped within said matrix.2. The spinal implant of claim 1, wherein said ceramic has acalcium/phosphorous ratio of between about 1.50 to about 1.60.
 3. Thespinal implant of claim 2, wherein said ceramic has acalcium/phosphorous ratio of about 1.51.
 4. The spinal implant of claim1, wherein said bone growth inductive factor is a bone morphogeneticprotein.
 5. The spinal implant of claim 4, wherein said bonemorphogenetic protein is selected from the group consisting of BMP-1,BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9, BMP-10, BMP-11,BMP-12 and BMP-13.
 6. The spinal implant of claim 5, wherein said bonemorphogenetic protein is a heterodimer of at least two BMPs selectedfrom said group.
 7. The spinal implant of claim 6, wherein saidheterodimer is a BMP-2 and BMP-7 heterodimer.
 8. The spinal implant ofclaim 4, wherein said bone morphogenetic protein is a bovine extractedBMP.
 9. The spinal implant of claim 1, wherein said implant has akidney-shaped cross-section to conform to the shape of vertebralendplates.
 10. The spinal implant of claim 1, wherein said body isrectangular-shaped.
 11. The spinal implant of claim 1, wherein saidimplant has a weight ratio of bone growth inductive factor to ceramic ofno more than about 1:200.
 12. The spinal implant of claim 11, whereinsaid implant has a weight ratio of bone growth inductive factor toceramic of between about 1:200 and about 1:2000.
 13. The spinal implantof claim 12, wherein said implant has a weight ratio of bone growthinductive factor to ceramic of about 1:1250.
 14. The spinal implant ofclaim 1, wherein said biphasic calcium phosphate ceramic has a pore sizefrom about 200 microns to about 600 microns.
 15. The spinal implant ofclaim 1, wherein said biphasic calcium phosphate ceramic has a porositybetween about 60% to about 80%.
 16. The spinal implant of claim 15,wherein said porosity of about 70%.
 17. The spinal implant of claim 1,wherein said biphasic calcium phosphate ceramic includes between about2-20% hydroxyapatite and about 80-98% tricalcium phosphate by volume.18. The spinal implant of claim 17, wherein said biphasic calciumphosphate ceramic includes between about 5-20% hydroxyapatite and about80-95% tricalcium phosphate.
 19. The spinal implant of claim 18 whereinsaid biphasic calcium phosphate ceramic includes about 20%hydroxyapatite and about 80% tricalcium phosphate.
 20. An osteoinductivecomposition comprising:a biphasic calcium phosphate ceramic carrierincluding between about 2-40% hydroxyapatite and about 98-60% tricalciumphosphate by volume; and a therapeutically effective amount of a bonegrowth inductive factor dispersed within said carrier for controlledformation of new bone within said carrier.
 21. The osteoinductivecomposition of claim 20, wherein said ceramic carrier includes between2-20% hydroxyapatite and between 80-98% tricalcium phosphate by volume.22. The osteoinductive composition of claim 21, wherein said ceramiccarrier includes between 5-20% hydroxyapatite and 80-95% tricalciumphosphate by volume.
 23. The osteoinductive composition of claim 22,wherein said ceramic carrier includes 20% hydroxyapatite and 80%tricalcium phosphate by volume.
 24. The osteoinductive composition ofclaim 20, wherein said ceramic carrier has a calcium/phosphorous ratioof between about 1.50 to about 1.60.
 25. The osteoinductive compositionof claim 24, wherein said ceramic carrier has a calcium/phosphorousratio of about 1.51.
 26. The osteoinductive composition of claim 20,wherein said bone growth inductive factor is a bone morphogeneticprotein.
 27. The osteoinductive composition of claim 26, wherein saidbone morphogenetic protein is selected from the group consisting ofBMP-1, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9, BMP-10,BMP-11, BMP-12 and BMP-13.
 28. The osteoinductive composition of claim27, wherein said bone morphogenetic protein is a heterodimer of at leasttwo BMPs selected from said group.
 29. The osteoinductive composition ofclaim 26, wherein said bone morphogenetic protein is a recombinant humanBMP.
 30. The osteoinductive composition of claim 26, wherein said bonemorphogenetic protein is a bovine extracted BMP.
 31. The osteoinductivecomposition of claim 20, wherein said composition has a ratio of bonegrowth inductive factor to ceramic of no more than about 1:200.
 32. Theosteoinductive composition of claim 31, wherein said composition has aratio of factor to ceramic of between about 1:200 to about 1:2000. 33.The osteoinductive composition of claim 32, wherein said composition hasa ratio of factor to ceramic of about 1:1250.
 34. The osteoinductivecomposition of claim 20, wherein said ceramic carrier is a body having aporosity between about 60% to about 80%.
 35. The osteoinductivecomposition of claim 34, wherein said porosity is about 70%.
 36. Theosteoinductive composition of claim 20, wherein said ceramic carrier isa body having a pore size from about 200 microns to about 600 microns.37. The osteoinductive composition of claim 20, wherein said ceramiccarrier is in granular form.
 38. A carrier for controlled delivery of abone growth inductive factor, comprising a porous biphasic calciumphosphate ceramic having between about 2-40% hydroxyapatite and about98-60% tricalcium phosphate, said ceramic having a calcium/phosphorousratio of between about 1.50 to about 1.60.
 39. The carrier of claim 38,wherein said ceramic has a calcium/phosphorous ratio of about 1.51. 40.The carrier of claim 38, wherein said ceramic is in the form of a bodyhaving a porosity between about 60% to about 80%.
 41. The carrier ofclaim 40, wherein said porosity is about 70%.
 42. The carrier of claim38, wherein said ceramic has a pore size from about 200 microns to about600 microns.
 43. The carrier of claim 38, wherein said ceramic includesbetween about 2-20% hydroxyapatite and about 80-98% tricalcium phosphateby volume.
 44. The carrier of claim 43, wherein said ceramic includesbetween about 5-20% hydroxyapatite and about 80-95% tricalcium phosphateby volume.
 45. The carrier of claim 44, wherein said ceramic includesabout 20% hydroxyapatite and about 80% tricalcium phosphate by volume.46. An implant, comprising:a porous ceramic body defining a confiningmatrix for confining new bone growth within said body; and atherapeutically effective amount of a bone growth inductive factorentrapped within said matrix at a weight ratio of bone growth inductivefactor to ceramic of no more than about 1:200.
 47. The spinal implant ofclaim 46, wherein said weight ratio is between 1:200 and 1:2000.
 48. Theimplant of claim 47, wherein said weight ratio is about 1:1250.
 49. Theimplant of claim 46, wherein said ceramic is a biphasic calciumphosphate ceramic.
 50. The implant of claim 46, wherein said bone growthinductive factor is a bone morphogenetic protein.